10 Alicyclic Compounds By B. T. GOLDING Department of Molecular Sciences University of Warwick Coventry CV4 7AL and A. P. JOHNSON The Polytechnic of North London Holloway Road London N7 806 1 Topographical Analysis General.-The proceedings of a symposium on conformational analysis held at Brussels in September 1969 have now been published. ‘y2 These publications provide an excellent survey of the current state of conformational analysis (or topographical analysis as Prelog3 suggests we should now call it). Calculations.-Several years ago Liehr‘ described some familiar terminology for conformers -twist-chair twist-boat etc.-as ‘mentally deficient’ and pleaded for its replacement by precise mathematical specifications. A relatively simple mathe- matical treatment has now been devised5 for cyclohexane which when coupled with calculations based on structural and vibrational data leads to conformational energy maps that provide a useful picture of the topological course of chair-chair interconversion.An important series of papers‘ describes the development of an improved force field for ‘molecular mechanics’ calculations and its application to the calculation of geometries and energies of a wide variety of hydrocarbons. The agreement achieved between computed and measured parameters is very im- pressive (bond lengths usually within 0.001 nm angles within lo). Strain energies were also assessed and their values agree well with those calculated by Schleyer [cf Aiinual Reports(B),1970,67,365] However Allinger‘ disagrees with Schleyer’s ‘ Various authors Piiw Appl.Chem. 1971 25 465-666. ‘Conformational Analysis Scope and Present Limitations,’ ed. G. Chiurdoglu Academic Press New York 197 1. V. Prelog p. 465 of ref. 1. A. D. Liehr J. Phys. Chem. 1963 67 471 (footnote 19). H. L. Strauss J. Chern. Ediic. 1971 48 221; H. M. Pickett and H. L. Strauss J. Amcr. Chem. Soc.. 1970 92 728 1. N. L. Allinger M. T. Tribble M. A. Miller and D. H. Wertz J. Aiuer. Chein. Soc. 1971 93 1637. i_ N. L. Allinger B. J. Gorden I. J. Tyminski and M. T. Wuesthoff J. Org. Chern. 1971 36 739. N. L. Allinger and M. T. Wuesthoff J. Org. Chein. 1971 36 2051. N. L. Allinger and F. Wu Tetrahedron,1971 36 739. 333 3 34 B. T. Golding and A. P. Johnson suggestion that across-ring C-C repulsions are the source of strain in cyclo- hexane and adamantane.According to Allinger,6 the main cause of this strain is repulsive vicical H-H interactions ( +0.42 kcal mol- each) and not C-C or C-H interactions since these are calculated to be slightly attractive (-0.13 and -0.05 kcal mol -I respectively). These effects render 1,3,5,7-tetramethyladamantane (calculated strain energy of 2.07 kcal mol-') less strained than adamantane (6.81kcal mol-I) whilst diamantane is much more strained (10.34 kcal mol- '). Allinger's group have also synthesized all possible perhydr~phenanthrenes~ and perhydroanthracenes,* and four androstanes' (5a,14a- 5a,14fi- 5/3,14a- and 5/3,14p-) [cf (1) which shows the 5a,14p isomer]. Relative energies within each group were measured by equilibration over palladium and compare favourably with calculated values (N.B.the order of stability found by both methods applied to androstanes is 5a,14P- > 5/?,14p-> 5a,14a-> 5/3,14a-).It is pointed outg that the calculations required 204 minutes of computer time for the androstanes were 10-100 times less expensive than the experimental work involved in their synthesis and equilibrations and gave structural parameters as a bonus. An excellent review" of the ab initio SCF LCAO MO method for the calcula- tion of conformations and their interconversion barriers has appeared. This method has been used to compute electron density maps for cyclopropane which illustrate well its bent bonds.' '*l Semi-empirical calculations (INDO type) suggestI3 that in a series of trans-2-vinylcyclopropylcarbinylderivatives (2) conjugation between the n-bond and the carbinyl centre is present in only one (2) R = Me CH,.CH2+,CF,' CF,. or BH case (2;R = CH +) but even then is of small magnitude. The MIND0/2 method has been used' to calculate activation energies for the degenerate rearrangements (constitutional topomerizations)' ' of bullvalene (3) barbaralene (4) and semi- bullvalene (5) [calculated values (experimental values bracketed) 11.3 (1 1.8 and 10 J.-M. Lehn in ref. 2 p. 129. I1 R. M. Stevens E. Switkes E. A. Laws and W. N. Lipscomb J. Ainu. Chern. Soc. 1971 93 2603. 12 H. Marsmann J.-B. Robert and J. R. Van Wazer Tetrahedron 1971 27 4377. 13 L.D. Kispert C. Engelman C. Dyas and C. U. Pittman J. Atner. Chem. Soc. 1971 93 6948. 14 M. J. S. Dewar and W. W. Schoeller J. Amer. Chem. SOC.,1971 93 1481. 15 See G. Binsch. E. L. Eliel and H. Kessler Angew Chem. Internal. Edn. 1971 10 570. 335 Alicyclic Compounds (3) X = CH=CH (4)X = CH (5) X = direct bond 12.8) 5.9 (8.6) and 2.3 (indeterminate by n.m.r.) kcal mol-' respecJively]. The decreaseinactivationenergyobservedonpassingfrom(3) to(4) to(5) i~suggested'~ to be due to increasing release of strain (cf:calculated distances r) and decreasing antibonding 1,4-interaction (cf distances s) in the transition state (6). The question is raised as to what modifications of semibullvalene might produce an isolable non-classical mesovalent system.r S 1.626 2.608 (3) 1.720 2.680 (4) 1.752 2.806 (5) Dewar14 implies that the calculations are so quick and reliable that they obviate synthetic exploration toward such molecules! In a later communication,' he presents the results of a calculation on a diazasemibullvalene which suggest that it will exist as the non-classical structure (7). In a beautifully illustrated paper by R. Hoffmann,' the problem of stabilizing a non-classical semibullvalene is explored using orbital symmetry arguments supported by extended Huckel F F calculations. It is concluded that a molecule of type (8) should be non-classical (as shown). A synthesis of either (7) or (8)is awaited with interest. Synthetic (and other) chemists may also find stimulation in an important paper'* entitled 'Symmetry topology and aromaticity' which considers many novel alicyclic structural types and their potential aromatic properties.Other Valence Tautornem.-The problem of explaining the position of the norcaradiene cycloheptatriene equilibrium in certain derivatives of the parent molecules continues to sustain interest [cf Annual Reports (B) 1970 67,3701. '' M. J. S. Dewar Z. Nahlovska and B. D. Nahlovsky Chern. Comm. 1971 1377 R. Hoffmann and W.-D. Stohrer J. Arner. Chern. SOC.,1971 93 6941. M. J. Goldstein and R. Hoffmann J. Arner. C'hem. So<,.,1971 93 6193. B. T. Golding and A. P.Johnson Whilst new equilibria have been discovered ' and octachlorocycloheptatriene has been shown to be a triene,20 perhaps the most intriguing current results are those of Roberts,21 who investigated equilibria between (9a) and (9b) (lOa) and (lob) and (lla) and (llb).Ar C0,Me 0 ?YMe (9a) Ar = Ph (9b) (10a) Ar = p-methoxyphenyl (lob) (lla) Ar = p-nitrophenyl (1 lb) The enthalpy for the reaction norcaradiene 3cycloheptatriene increases in the order (10) < (11) < (9). Roberts2' concludes that none of the existing theories ex- plain his results convincingly. A study22of equilibria in barbaralones has given A B (12) R' = D,R2 = H (55.5XB) (13) R' = H R2 = Me (B predominates) (14) R' = Me R2 = H (76.6% A) (1 5) R' = H R2 = D (A predominates) the results shown [(12H15)],for which an explanation is promised. The 'H n.m.r. spectroscopic properties of dimethyl cyclo-octatetraene- 1,2-dicarboxylate are con- ~istent~~ with the dominance of conformer (16) over (1 7).When the diacid (I 8) R' (16) R' = H R2 = R3 = C02Me @)--~2 (17) R3 = H,R' = R2 = C0,Me (18) R' = H,R2 = R3 = C02H (19) R3 = H,R'R2 = -CO-O-CO- R3 '' W. Betz and J. Daub Angew. Chem. Internat. Edn. 1971 10. 269 H. Diirr and H. Kober ibid. p. 342; H. Giinther B. D. Tunggal M. Regitz H. Scherer and T. Keller ibid.,p. 563. K. Kusuda. R. West and V. N. M. Rao J. Amer. Chem. SOC.,1971. 93 3627. 21 G. E. Hall and J. D. Roberts J. Amer. Chetn. SOC.,1971 93 2203; see also E. Ciganek ibid. p. 2207. 22 J. C. Barborak S. Chari and P. von R. Schleyer J. Amer. Chetn. SOC.,1971 93 5275. 23 D. Bryce-Smith A.Gilbert and J. Grzonka Angew. Chem. Infernat. Edn. 1971 10 746. Alicyclic Compounds 337 is treated with dicyclohexylcarbodi-imideit forms the corresponding anhydride which is unstable but does not rearrange to (19). Structure Determination.-Mainly by N.M.R . Spectroscopy. Reviews have been published on double-resonance technique^,^^ on 3C n.m.r. spectroscopy,2 and on the nuclear Overhauser effect,26 and include many examples of applications in the field of alicyclic chemistry. Using an approach based on the McConnell equation Allinger and his co-~oikers~~ have developed a successful semi- empirical method for calculating chemical shifts in hydrocarbons [cf.observed and calculated data for norbornane (20)]. 'Its improvement over earlier approaches lies in the recognition of the importance of van der Waals effects.Among the glut of papers on shift reagents are reports of useful new reagent^^',^^ and some instructive application^.^'-^^ There has been a degree of uncertainty with respect to the positioning of a lanthanide atom relative to a molecule under examination. It has now been shown3 that non-linear regression analysis permits an estimation of that position of the lanthanide which gives the best fit when the shift data are plotted against (3cos2 8 -l)r-3. In this way excellent linear correlations were obtained for shifts induced by Eu(tmhd),* with ada- mantan-2-01 and trans-4-t-butylcyclohexanol.This technique may be useful in structure determination. The importance of the angle factor is illustrated by specific upfield shifts of H(3') and H(4')caused by Eu(tmhd) with the cis-isomer of 3-(cr-naphthyl)-1,3,5,5-tetramethylcyclohexanol, which therefore exists as con- former (2 ICH 6 1.21 (calcd.1.195) H 1.49 (1.341) H 1.18(1.257) Since the range of I3C chemical shifts is approximately 10 times greater than that of protons it is more likely that distinct signals will be observed for con- 24 W. von Philipsborn Angew. Chern. Internat. Edn. 1971,10,472. " E.Breitmaier G. Jung and W. Voelter Angew. Chem. Internat. Edn. 1971 10,673; E.W. Randall Chem. in Britain 1971 371. *' G.E. Bachers and T. Schaefer Chem. Rev. 1971,71,617. *' M. T. Tribble M. A. Miller and N. L. Allinger J. Amer. Chem. SOC.,1971,93 3894. 2n J. K.M. Sanders and D. H. Williams J. Amer. Chem. Soc. 1971,93 641. 29 R. E. Rondeau and R. E. Sievers J. Amer. Chem. SOC.,1971,93 1522. 30 R. von Ammon R. D. Fischer and B. Kannelakopulos Chem. Ber. 1971,104,1072. 31 S.Farid A. Ateya and M. Maggio Chem. Comm. 1971 1285. 32 B. L. Shapiro J. R. Hlubucek G. R. Sullivan and L. F. Johnson J. Amer. Chem. Soc. 1971,93 3281. * tris-(2,2,6,6-tetramethylheptanedionato)europium. 338 B. T. Golding and A. P. Johnson formational isomers under conditions of slow exchange. With this in mind and helped by a variable-temperature Fourier-transform instrument the axial con- former of methylcyclohexane could be detected at -110"C.33 On cooling from -65 to -162 "C the I3C n.m.r. spectrum of cyclononane changes from a single peak to two sharp singlets (ratio 1 :2) separated by 8.9~.p.m.~~ This is consistent with the dominance of the TBCconformer (22) assuming that fortuitous equivalence is not concealing signal(s) from other conformer(s).The TBC form is that independently calculated by Hendrickson Lifson and Allinger* to be most stable [cf also Annual Reports (B),1970,67 371 and the results of an X-ray study on cyclononanone-HgCI reported below]. Low-temperature 3C n.m.r. spectro- scopy has also been used3 to study conformational inversion in dimethylcyclo- hexanes cis-decalin and cis-9-methyldecalin. Quantitative measurements of exo-endo equilibria in norbornanes that the conformational free energy differences for the groups Me (0.89 kcal mol-I) OH (1.05),CO,Me (0.65) and NO (1.38) bear no relationship to their A-values (1.70,0.95 1.27 and 1.20 kcal mol- ',respectively).A new compilation of A-values is available3 [recent A-value determinations include those for azido- (0.80 f0.06 kcal mol- in CS,),38 trimethylsilyloxy- (0.89 kcal mol- 1),39 and phthalimido-groups (3.8-3.9 kcal mol- By careful measurement of coupling constants and using the Karplus equation to derive dihedral angles two gro~ps~',~' have attempted to determine the in-fluence of bulky substituents on the shape of the cyclohexane ring in solution. Booth and Thornburrow4' interpret their results for a series of cis-l-substituted-4-phthalimido-cyclohexanes in terms of ring flattening. A Dutch group4 explain their results for t-butylcyclohexane by postulating increased puckering at the t-butyl 'end' which causes H(l) to lean inwards.This effect is not seen with methylcyclohexane (23) but both this compound and t-butylcyclohexane (24) show a substantial upfield shift for H(2,) [actual chemical shifts 6 0.90 for (23) 0.87 for (24); cf 1.20 for cyclohexane]. In the case of (24) but not (23) H(4,) is also shifted upfield (appears at 6 1.10). The shift for H(2,) is not convincingly rationalized whilst that for H(4,) again shakes one's confidence in the practice of assessing chemical shifts in equilibrating conformers by using those in the corre- sponding 'frozen' t-butyl derivatives. Dissolution of several 2-halogeno- and 2,6-dihalogeno-cyclohexanonesin a 'superacid' medium at -60 "C has a remarkable effect on their conformational preferences because of the creation of a strong hydrogen-bond which bridges " F.A. L. Anet C. H. Bradley and G. W. Buchanan J. Amer. Chrin. Soc. 1971,93 258. 34 F. A. L. Anet and J. J. Wagner J. Aiwr. Cheiri. Soc. 1971 93 5266. 35 D. K. Dalling D. M. Grant and L. F. Johnson J. Amer. Chein. SOC. 1971 93 3678; H.-J. Schneider R. Price and T. Keller Angew. Chrm. Inrprnat. Edn. 1971 10. 730. 36 R. J. Ouellette J. D. Rawn and S. N. Jreissaty J. Amer. Chem. Sor. 1971 93 71 17. 37 F. R. Jensen and C. H. Bushweller Adu. Alicyciir Chem. 1971 3 139. 38 D. N. Jones K. J. Wyse and D. E. Kirne J. Chein. SOC.(C),1971 2763. 39 J. P. Hardy and W. D. Curnming J. Atner. Chetn. SOC.,1971 93 928. H. Booth and P. R. Thornburrow J.Chem. SOC.(B) 1971 1051. " J. D. Rernijnse H. Van Bekkum and B. M. Wepster RPC'.Trui,.chim. 1971 90 779. * c-1footnotes 5-7 in ref. 34. Alicyclic Compounds 339 oxygen to halogen.42 For example 2-fluoro-6-methylcyclohexanone ordinarily prefers to exist as conformer (25) but is converted into (26) on protonation. Certain trans-isomers [e.g. (27)] of 2-alkyl-2-methyl-4-t-butylcyclohexanones fluoresce more strongly than the corresponding cis-isomers because intra- molecular y-hydrogen abstraction which deactivates the S state of the ketone occurs more easily in the cis-i~omer.~~ This promises to be a useful method for structure determination in a specific area. .. F .H'+ Me (25) By Electron and Neutron Difraction X-Ray Crystallography and Microwave Spectroscopy.A large number of exact structure determinations have been carried out (e.g. refs. 44-57). Among notable features of the findings are the following :the F-C -F angle (1 12.2") in hexafluorocyclopropane is smaller than the H-C-H angle in cyclopropane (115.1°) but accords with the expectation that the electronegative fluorine atoms will decrease the s-character of the hybrids at carbon directed towards F;44two four-membered rings in (28) are puckered whilst the others are planar46 (this paper contains a useful summary of 42 R. Jantzen and J. Cantacuzene Tetrahedron Letters 197 1 2925. 53 K. Dawes N. J. Turro and J. M. Conia Tetrahedron Letters 1971 1377. 54 J. F. Chiang and W. A. Bernett Tetrahedron 1971 27 975.45 H. J. Mair and S. H. Bauer J. Phys. Chem. 1971 75 1681 (perchlorocyclopropene). 46 J. P. Schaefer and K. K. Walthers Tetrahedron 1971 27,5281. 47 H. J. Geise and F. C. Mijlhoff Rec. Trac. chirn. 1971 90 577. an J. W. Bevan and A. C. Legon Chern. Cotnm. 1971 1136. 4') C. H. Chang and S. H. Bauer J. Phys. Chem. 1971 75 1685 (perfluoro- and per- chlorocyclopentadiene). 50 H. J. Geise H. R. Buys and F. C. Mijlhoff J. Mol. Siructure 1971 9 447 (cyclohexane and methylcyclohexane). 51 V. J. James and J. F. McConnell Tetrahedron 1971 27 5475. 52 D. H. Faber and C. Altona Chern. Camrn. 1971 1210. s3 S. Dahl and P. Groth Acta Chern. Scund. 1971 25 1114. 51 0. Ermer and J. D. DunitL Chern. Cornrn. 1971 178. 55 A. Almenningen B. Andersen and B.A. Nyhus Acra. Chern. Scund. 1971 25 1219. 56 A. Yokozeki and K. Kuchitsu Birll. Chetn. SOC.Japan 1971 44 1783. 57 0. Ermer R. Gerdil and J. D. Dunitz Helv. Chim. Actu 1971 54 2476. 340 B. T. Golding and A. P.Johnson X-ray structural data for cyclobutanes) ; cyclopentanone is less puckered than cyclopentane ;47 cyclopent-3-enone is flat ;48 there is slight ring-flattening in cyclohexyl toluene-p-sulphonate ;5 in cis7trans-2,5-di-t-butylcyc10hexy1 toluene-p-sulphonate the H atoms at C(2) and C(5) tilt towards the centre of the ring in order to allow unusually large exocyclic angles (1 13-1 18")to the t-butyl groups and there is imperfect staggering about the C(2)-But and C(S)-Bu' bonds;52 in its 1 1 adduct with HgCl, cyclononanone is present as the TCB form (29)53 (c$ discussion on cyclononane on p.338); neutron diffraction analysis reveals a transannular separation of 0.191 nm between two hydrogen atoms in cyclo- decane-176-diol;54 another electron diffraction study of bicycle[ l,l,l]pentane has given results55 at variance with those previously reported [see Anrzual Reports (B) 1970 67 3721; bicyclo[2,2,2]octene and bicyclo[2,2,2]octadiene both have C, symmetry ;56 the structure of [4,4,4]propellane is all-chair but the central C-C bond (0.1556 nm) is significantly longer than Information on ring puckering inversion barriers and conformational energies has been gained from i.r. and Raman studies of some derivatives of cy~lobutane,~~ and bromo- and chloro-cyclopentane.60 cyclopentan01,~~ 2 Synthesis Novel Hydrocarbons.4ne of the recurrent themes in the synthesis of alicyclic compounds has been the search for new hydrocarbons possessing structural features which promise exceptional reactivity.The past year has seen further progress in this area. The pioneering work of van Tamelen which led to the synthesis of Dewarbenzene,61 bicycl0[2,1,O]pent-2-ene,~~ and cyclodecapenta- ene63 in the sixties has now been fully described. Other compounds of this ilk whose synthesis has been claimed include A'*4-bicyclo[2,2,0]hexene(30),which can be detected spectroscopically at -52 "C (and trapped by cyclopentadiene) but which dimerizes to (31) at -20 0C;64A'.2-bicyclo[2,2,1]heptene (eroding still further Bredt's rule) which cannot be isolated but can be trapped by furan ;65 and 1-methylpentalene (32) which can be detected spectroscopically at -196°C but dimerizes at -100°C.66 A simple new route to benzvalene (33) utilizes the reaction of lithium cyclopentadienide with methylene chloride and methyl-lithi~m.~~ While this route permits the preparation of (33) in bulk this should only be attempted with expendable co-workers since even '' F.A. Miller and R. J. Capwell Spectrochitn. Acta 1971 27A 11 13; J. R. Durig and W. C. Harris ibid. 649; J. R. Durig J. N. Willis and W. H. Green J. Chem. Phys. 197 1 54 1547. 59 J. R. Durig J. M. Karriker and W. C. Harris Spectrochirn. Acta 1971 27A 1955. 6o W. C. Harris J. M. Karriker and J. R. Durig J. Mol. Srructure 1971 9 139. 61 E.E. van Tamelen S. P. Pappas and K. L. Kirk J. Ainer. Chern. Sac. 1971 93 6092. 62 E. E. van Tamelen J. I. Brauman and L. E. Ellis J. Atner. Chem. Sac. 1971 93 6145. 63 E. E. van Tamelen and R. H. Greeley Chem. Comm. 1971; 601; E. E. van Tamelen and B. C. T. Pappas J. Amer. Chem. Soc. 1971 93 61 11 ; E. E. van Tamelen T. L. Burkoth and R. H. Greeley ibid. p. 6120. 64 K. B. Wiberg G. J. Burgmaier and P. Warner J. Amrr. Chem. SOC.,1971 93 246. " R. Keese and E.-P. Krebs Angew. Chetn. Internat. Edn. 1971 10 262. 66 R. Bloch R.A. Marty and P. de Mayo J. Atner. Chern. Soc. 1971 93 3071. 6' T. J. Katz E. J. Wang and N. Acton J. Amer. Chem. SOC.,1971 93 3782. Alicyclic Compounds 341 m 8 small quantities of (33) can explode violently. Cycloheptyne itself enjoys only a fleeting existence but a substituted cycloheptyne (34) has now been shown to be more stable.Oxidation of the bis-hydrazone (35) leads to (34) which has a half- life of one day in solution (0.2mol I-' in CC1,).68 Me 0H NNH Me Me Me Me The isolation of the [lOIannulenes (36) and (37) in the crystalline state by Masamune and his collaborators is a superb practical a~hievement.~~ These compounds were prepared by a modification of an earlier procedure and isolated by chromatography at -80 "C! Their properties indicate that they are clearly not aromatic. Other (CH), hydrocarbons which have been synthesized for the first time are (38) (39) and (40). Tricyc10[4,4,0,0~,~]deca-3,7,9-triene (38) is thought to be a key intermediate in the thermal rearrangements of several (CH), hydrocarbons.It was synthesized by a route which might be extended to permit the synthesis of other compounds which are formally Diels-Alder adducts of A. Krebs and H. Kimling Angew. Chern. Internat. Edn. 1971 10 509. 69 S. Masarnune K. Hojo K. Hojo G. Bigam and D. L. Rabenstein J. Amer. Chem. SOC.,1971 93 4966. B. T. Golding and A. P. Johnson benzene.70 'Hypostrophene' (39) was prepared by the action of sodium on (41),7 which was itself prepared in several steps from cyclobutadieneiron tricarbonyl and benzoquinone. (39) undergoes a degenerate Cope rearrangement at 35 "Cwhich has been detected by deuterium labelling. (40) is a bridged cis-trishomobenzene which was synthesized by irradiation of the bridged bishomo- barrelene (42).7 On warming (40) undergoes a cycloreversion to quinacene (43).(41) (42) (43) With the reported synthesis of [2O]ann~lene~~ (which is of course not aromatic) all the annulenes up to [24]annulene have now succumbed to attempts to synthesize them.74 Other Systems.-General. Enone pho toannelation free-radical c ycli~ations,~ the synthetic uses of halogenated keten~,~~ and the synthesis of adamantanes and related hydrocarbons have been reviewed.78 Three-and Four-membered Rings. Modifications which increase the utility of the Simmons-Smith reaction are always welcome and this includes the finding that the presence of oxygen appreciably increases both the rates and yields of olefin cyclopropanation by the methylene iodide-diethylzinc system.79 Substituted cyclopropanes are formed in moderate yield from the reaction of a-chloro- ketones -esters or -nitriles with electron-deficient olefins in the presence of a copper(I) oxide -isonitrile complex.80 Further examples of the usefulness of quaternary ammonium halides in facilitating cyclopropanation with halogenb- alkane-base combinations have appeared.81*82 Thus chloroform aqueous sodium hydroxide and a catalytic quantity of triethylammonium chloride give high yields of dichlorocyclopropanes from olefins such as trans-stilbene which fail to react with potassium t-butoxide-chloroform.82 A new cyclopropane synthesis is initiated by Michael addition of acidic methy- lene compounds to (dimethylamino)phenyI-(2-phenylvinyl)oxosulphoniumfluo-70 E.Vedejs Chem. Comm. 1971 536. 71 J. S. McKennis L. Brener J. S. Ward and R. Pettit J. Amer. Chem. Soc. 1971 93 4957. 72 A. de Meijere D. Kaufmann and 0. Schallner Angew. Chem. lnrrrnut. Edn. 1971 10 417. 73 B. W. Metcalf and F. Sondheimer J. Amrr. Chem. Soc.. 1971. 93 6675 74 R. M. McQuilkin B. W. Metcalf and F. Sondheimer Chem. Comm. 1971 338; F. Sondheimer Pure Appl. Chem. 1971 28 331. 75 P. de Mayo Accounts Chem. Res. 1971 4 41 16 M. Julia Accounts Chem. Res. 1971 4 386. 7' W. T. Brady Synthesis 1971 415. 7n R. C. Bingham and P. von R. Schleyer Forrschr. Chem. Forsch. 1971 18 1. 79 S. Miyano and H. Hashimoto Chem. Cornm. 1971 1418. no T. Saegusa Y. Ito K. Yonezawa Y. Inubushi and S.Tomita J. Atner. Chem. SOC. 197 1 93 4049. 81 M. Makosza and E. Bialecka Tetrahedron Letters 1971 4517. 82 E. V. Dehmlow and J. Schonefeld Annulen 197 1 744 42. A licyclic Compounds Ph H H A C0,Me H-Ac02 343 Me M++O HS Ph CN Ph' "Me2 (45) n R'CO CH=CH (46; R' = Me or Ph; R2 = H Me or Ph) roborate (44);83e.g. (44) reacts with methyl cyanoacetate and base to give (45). cis-8-Ketols of the type (46) are dehydrated in acid to give cis-vinylcyclopropyl ketones (47).84Irradiation of the polyacetylene (48) leads to the epimeric cyclo-propanes (49).8 Other ally1 chlorides where the double bond is conjugated with an alkyne grouping behave similarly. MeCH =CH[C C] C H =CHCHCH 0Ac I 3 CI MeCH=CH[C-C]; 'CH,OAc A useful addition to the established photochemical routes to cyclobutanes is the synthesis of acylcyclobutanes from certain a-methylene ketones ; e.g.(50) gives (51).86 The lithium-iodide-catalysed rearrangement of methylenecyclopropane epoxide provides a mild route to cy~lobutanone.~~ Cyclobutenone88 and cyclob~tenedione~~ have been prepared for the first time the latter by hydrolysis of (52) the product of photoaddition of acetylene to dichlorovinylene carbonate. 0 0 CI " C. R. Johnson and J. P. Lockard Tetrahedron Letters 1971 4589. n4 Y. Bahurel F. Collonges A. Menet F. Pautet A. Poncet and G. Descotes Bull. Soc. chim. France I97 I 2209. 8s F. Bohlmann W. Skuballa C. Zdero T. Kuhle and P. Steirl Annalen 1971 745,176. 86 W. L. Schreiber and W.C. Agosta J. Amer. Chem. SOC.,1971 93 6292. " J. R. Salaiin and J. M. Conia Chem. Comm. 1971 1579. 88 J. B. Sieja J. Amer. Chem. SOC.,1971 93 2481. 89 J. C. Hinshaw Chem. Comm. 1971 630. 344 B. T. Golding and A. P.Johnson Five- und Six-membered Rings. The compound (53) is a key intermediate in one of Corey's prostaglandin syntheses. A new high-yield procedure for its synthesisg0 uses the reaction of chloromethyl methyl ether with thallous cyclopentadienide a method which avoids prototropic rearrangements. The base-induced conversion of 2-chlorocyclohexane- 1,3-diones to 2-cycl~pentenones~ is a useful variation of an older cyclopentanone synthesis. The pyrolytic conversion of (54) into (55) by a retro-Diels-Alder reaction provides another versatile synthesis of 2-cyclopen- ten one^.'^ (55)isomerizes to (56) in the presence of acid or base.Dialuminium- substituted cyclopentyl derivatives (57)are available via the hydroalumination of Me S2OMe +; .;i.. RI(R~) R' 0 (53) 0' R2 (54) R1 = R2 = H or R' = H R2 = Me or R' = H R2 = CH -Et he~-l-en-Syne.~~ Because of the reactivity of the C-A1 bond compounds of this type should become useful synthetic intermediates. Electrochemical reduction of non-conjugated ketones such as (58;n = 3 or 4) leads to tertiary alcohols (59) with a high degree of stereoselectivity ;94 e.g. hept-6-en-2-one forms (60) ex-clusively. yH,AIR2 R 'CH =CH( CH 2),C0R2 0"'"' (58) R2 \ JCH,)" ,c CHCH,R' HO (59) '" E.J. Corey U. Koelliker and J. Neuffer J. Atizrr. Clzetn. Soc. 1971 93 1489. 91 G. Biichi and B. Egger J. Org. Chern. 1971 36 2021. 92 G. Stork G. L. Nelson F. L. Rouessac and 0. Gringore J. Alner. Chern. Soc. 1971 93 3091. 93 G. Zweifel G. M. Clark and R. Lynd Chem. Comm. 1971 1593. 94 T. Shono and M. Mitani J. Amrr. Ctietn. Soc. 1971 93 5284. Alicyclic Compounds Large Rings. The oxy-Cope rearrangement has been used to synthesize large carbocyclic rings but the yields are often low. A new high-yield variation is the siloxy-Cope rearrangement ;9 e.g. pyrolysis of (61)followed by hydrolysis yields undec-7-enone (62) as a mixture of geometrical isomers. Two new routes96 to macrocyclic ketones begin with the methyl enol ether of cyclododecanone.The size of the ring can be increased by either two or four carbon atoms as shown in Scheme 1. The key step in the two-carbon expansion is a photo-induced 1,3-acyl migration. .OMe Reagents i 2-methylbut-3-yn-2-ol-toluene-p-sulphonic acid; ii hv; iii vinylmagnesium bromide iv 350 “C Scheme 196 Bicyclic and Polycyclic Systems. A number of substituted bicyclobutanes have been prepared by base-induced elimination of HCl from chlorocyclobutanes such as (63; X = CN CO,R CONH, or COR).97 The action of magnesium on (63;X = OEt) leads to the parent bicy~lobutane.~~ The cyclopropyl-sulphonium ” R. W. Thies Chrm. Cow~nz.,1971 237. 96 R. C. Cookson and P. Singh J. Chem. Soc. (C),1971 1477. 97 H. K. Hall jun. E. P. Blanchard jun. S.C. Cherkofsky J. B. Sieja and W. A. Sheppard J. Amer. Chem. Soc. 1971 93 110; H. K. Hall jun. C. D. Smith E. P. Blanchard jun. S. C. Cherkofsky and J. B. Sieja ibid. p. 121. ” J. B. Sieja J. A/iier. Chem. Soc. 1971 93 130. B. T. Golding and A. P.Johnson and -sulphoxonium ylides (64)9g and (65)"' react with @unsaturated ketones to form spiropentane products; e.g. (65) with mesityl oxide gives (66)."' An improved method for the 1,4-addition of the methyienecarbonyl unit (-CH,CO-) to dienes is shown in Scheme 2."' The yields at each stage are almost quantitative. The l-hydroxy-7-methylenebicyclo[3,2,l]octane system ZCH ZCH, g2z cly""':' i+&&-& 0 Z = OMe OCH,Ph or NHCOPh Reagents i 0 "C 18 h; ii NaN, dimethoxyethane 25 "C;iii reflux; iv HOAc-H,O 55-60 "C.Scheme 2lo' has aroused much interest because of its presence in the gibberellins. The key step in a new synthetic approachlo2 to this system is the solvolysis of (67) to (68) the former being prepared by photoannelation. Photosensitized cycloaddition of dichlorovinylene carbonate to benzene leads to (69) which yields the hitherto unknown bicyclo[2,2,2]octadiene-2,3-dione(70) on hydroly~is.''~ Consecutive enamine alkylations form the basis of a new synthesis of spiro- cyclic ketones.lo4 An example of the process is the stereospecific conversion of (71) into (72) by the action of (73). 99 B. M. Trost and M. J. Bogdanowicz J. Amer. Chem. Soc. 1971 93 3773. loo C. R. Johnson G. F. Katekar R. F. Huxol and E. R. Janiga J.Amer. Chem. Soc. 1971 93 3771. lo' E. J. Corey T. Ravindranathan and S. Terashima J. Amer. Chem. Soc. 1971 93 4326. lo' F. E. Ziegler and J. A. Kloek Tetrahedron Letters 1971 220 1. '03 H.-D. Scharf and R. Klar Tetrahedron Letrers 1971 517. lo4 D. J. Dunham and R. G. Lawton J. Amer. Chem. Soc. 1971,93 2074. Alicyclic Compounds Fresh aspects of the Robinson-Mannich annelation continue to be un-covered. In the preparation of (74) from but-3-en-2-one and 2-methylcyclo- pentane-1,3-dione the use of natural amino-acids as catalysts for the cyclization step leads to optically active (74) with optical purity of up to 84%.'05 The (S)-enantiomer predominates when (S)-amino-acids are employed. Although in the past the reaction of trans-pent-3-en-2-one with unactivated cyclohexanones such as 2-methylcyclohexanone has proceeded poorly under the usual reaction conditions the use of the preformed sodium enolate of 2-methylcyclohexanone gives a high yield of (75) and (76).'06 The stereoselectivity of the reaction is very (75) R' = Me R2 = H (77) (76) R' = H RZ= Me high and remarkably solvent dependent the isomeric purity of the product being greater than 95% with either dioxan or dimethyl sulphoxide as solvent.The cis-product (75) predominates in the former case and the trans-product (76) in the latter possibly because of the operation of the mechanism shown in Scheme 3 where the role of the dimethyl sulphoxide is to facilitate proton transfer. The stereochemical outcome of the reaction between (77) and trans-pent-3-en-2-one is also markedly solvent dependent,"' the cis-product (78) predominating in tertiary alcohols at low temperature and the trans-product in aprotic solvents.Several hydroazulene syntheses have been reported and some are summarized in Scheme 4. lo5 U. Eder G. Sauer and R. Wiechert Angew. Chem. Internat. Edn. 1971 10 496. Io6 C. J. V. Scanio and R. M. Starrett J. Amer. Chem. SOC.,1971 93 1539. lo' J. A. Marshall and T. M. Warne jun. J. Org. Chem. 1971 36 178. B. T. Golding and A. P.Johnson 1 Scheme 3 H Ref. 108. P 03 H R R OAc Ref. 109. R = H Ref. 110. R = Me Scheme Aontinued on next page lo* J. B. Hendrickson and R. K. Boeckman jun. J. Amer. Chem. Soc. 1971,93 1307 Io9 C.J. V. Scanio and L. P. Hill Chetn. Comm. 1971 242. ‘lo J. A. Marshall and A. E. Greene Tetrahedron Letters 1971 859. Alicyclic Compounds 349 C0,Me Ref. 112. & a H2C Me 0 Reagents i MeI; ii OH-; iii HOAc; iv ION-HC1; v polyphosphoric acid; vi MeO-; vii 380 "C Scheme 4 Intramolecular transfer of methylene seems to be involved in the stereospecific base-induced conversion of (79) to (80).' ' The functionality of compounds such as (80) should make them useful synthetic intermediates. Intramolecular acid- catalysed alkylations by diazoketones are also potentially useful cyclization processes; e.g. (81) gives (82)'14 and (83) gives (84).'" + ,S-Me COCH=N2 Me 'I' G. L. Buchanan and G. A. R. Young Chem.Comm. 1971 643. R. A. Kretchmer and W. J. Frazer J. Org. Chem. 1971 36 2855. ' l3 R. S. Matthews and T. E. Meteyer Chem. Comm. 1971 1576. D. J. Beames T. R. Klose and L. N. Mander Chem. Comm. 1971 773. 'Is W. F. Erman and L. C. Stone J. Amer. Chem. Soc. 1971 93 2821. B. T. Golding and A. P. Johnson Biogenetic-like olefin cyclizations are now well established. As shown in Scheme 5 participation of an acetylenic bond in such cyclizations is a useful modification the resulting vinylcarbonium ion being trapped to give a ketone or masked ketone. Further examples of cycloalkanone synthesis by intramolecular OH I (a) HCO,H R = OCHO (b) MeCN-CF,CO,H R = NHCOCH Et I OH i Formic or trifluoracetic acid Ref. 117. t ii Hydrolysis :5" Ratios vary between 60 :40 and 80 20 Scheme 5 alkylation of chloro-olefins are reported [cf Annual Reports (B),1970 67 3741.The acid-catalysed conversion of (85)into a 2 :1 mixture of (86) and (87) shows the utility and stereoselectivity of this process.' Diamondoid hydrocarbons such as adamantane are usually prepared by isomerization of other hydrocarbons. The specificity and yield in this process can 'I6 W. S. Johnson M. B. Gravestock R. J. Parry R. F. Myers T. A. Bryson and D. H. Miles J. Arner. Chem. SOC.,1971 93 4330. 'l7 P. T. Lansbury and G. E. DuBois Chem. Comm. 1971 1 107. 'I8 P. T. Lansbury P. C. Briggs T. R. Demmin and G. E. DuBois J. Amer. Chem. Soc. 1971 93 131 1. Alicyclic Compounds 35 1 be markedly improved if chlorinated platinum-aluminium catalysts are employed instead of the usual Lewis acids."' Barton and his co-workers have published details of their synthetic approach to the tetracyclines.12' One of the many impressive reactions therein is the acid- catalysed photocyclization of (88)to (89) via the hexatriene (90).0 TlH Ph 0 OCH,CH,OH 3 Reactions Metal-promoted Transformations.-Last year we indicated the upsurge of activity in this field which has led to the discovery of many new reactions [see An-nual Reports (B) 1970,67,399]. There was some uncertainty however regarding 'I9 D. E. Johnston M. A. McKervey and J. J. Rooney J. Amer. Chem. Soc. 1971 93 2798. I2O D. H. R. Barton and P. D. Magnus J. Chern. Soc. (C) 1971 2164; D.H. R. Barton B. Halpern Q. N. Porter and D. J. Collins ibid. p. 2166; E. Aufderhaar J. E. Baldwin D. H. R. Barton D. J. Faulkner and M. Slaytor ibid. p. 2175; J. E. Baldwin D. H. R. Barton N. J. A. Gutteridge and R. J. Martin ibid. p. 2184; D. H. R. Barton D. L. J. Clive P. D. Magnus and G. Smith ibid. p. 2193; D. H. R. Barton L. Bould D. L. J. Clive P. D. Magnus and T. Hase ibid. p. 2204; D. H. R. Barton P. D. Magnus and T. Hase ibid. p. 2215; D. H. R. Barton P. D. Magnus and M. J. Pearson ibid. pp. 2225 2231; D. H. R. Barton (Mrs.) J. A. Challis P. D. Magnus and J. P. Marshall ibid. p 2241. 352 B. T. Golding and A. P.Johnson the mechanisms of catalysis. The proposal that the metals promote reactions by relieving orbital symmetry constraints within the organic substrate has been re- iterated'" for some reaction-types (2 + 2 cycloadditions and reversions).A qualitative rule has been proposed :'22 'Transition metals may catalyse pericyclic reactions if and only if they involve antiaromatic transition states' (in the uncatalysed reaction). For metal-catalysed rearrangements of bicyclo[l,l ,O]-butane tricyclo[4,1 ,0,OZy7]heptane (91) and their alkyl derivatives much experimental evidence now shows that these are stepwise reactions. In the presence of a catalytic amount of silver(1) ions endo,exo-2,4-dimethyIbicyclo[ l,l,O]butane (92) gives cis,trans-hexa-2,4-diene (93) [99 % at 5 "C] whilst the exo,exo-isomer (94)gives mainly the trans,trans-diene (95) [73 % + 22 %cis,trans-diene (93)]' 23,1 24 [in thermolyses (92) +(95) and (94) -+ (93)].Although this behaviour might be expected from one-step reactions proceeding under orbital symmetry control a kinetic analysis of the reaction of tricyclo[4,1 ,0,02.7]heptane (9 I) giving cis,cis-cyclohepta-1,3-diene in the presence of silver(1) ions showed that at least one intermediate must be involved.' 24 (91) R' = R4 = H R2R3 = -(CH2)3-(92) R' = R3 = H R2 = R4 = Me (94) R2 = R3 = H R1 = R4 = Me Meanwhile at Ohio within shouting distance of Paquette Gassman and his students were studying the rearrangements of bicyclo[l,l,0]butanes and tri- cyclo[4 1,0,02.7]heptanes catalysed by other metal ions.' 5-' 29 The nature of the products formed is very dependent on the metallic catalyst used (cf.Scheme 6).Gassman suggests'29 that the metal ion functions as a very selective Lewis acid which triggers the transformations shown in Scheme 7. An earlier suggestion of catalysis by a Lewis acid was made in connection with the rearrange- ment of 1,2,5-tri-t-butylprismane (96) to 1,2,5-tri-t-butylbicyclo[2,2,0]hexa-2,4-diene (97) and other products which is catalysed by a host of metallic reagents and even by 1,3,5-trinitrobenzene.' I2l F. D. Mango and J. H. Schachtschneider J. Amer. Chetn. Soc. 1971 93 1123. 122 M. J. S. Dewar Angew. Chem. Internat. Edn. 1971 10 761 "' M. Sakai H. Yamaguchi H. H. Westberg and S. Masamune J. Amer. Chern. Soc. 1971,93 1043. 12' L. A. Paquette S. E. Wilson and R. P. Henzel J. Amer. Chem. Soc. 1971 93 1288. P. G. Gassman and F.J. Williams J. Arner. Chem. SOC.,1970 92 7631. '26 P. G. Gassman G. R. Meyer and F. J. Williams Chem. Comm. 1971 842. "' P. G. Gassman and T. J. Atkins J. Amer. Chem. SOC., 1971 93 1042. lZ8 P. G. Gassman T. J. Atkins and F. J. Williams J. Amer. Chem. Soc. 1971 93 1812. 129 P. G. Gassman and T. J. Atkins J. Amer. Chem. Soc. 1971 93 4597. I3O L. A. Paquette R. P. Henzel and S. E. Wilson J. Amer. Chem. Soc. 1971 93 2335. 13' K. L. Kaiser R. F. Childs and P. M. Maitlis J. Amer. Chern. SOC.,1971 93 1270. Alicyclic Compounds Scheme 6 1"' 1 1-M" v 9 H Scheme 7 B. T. Golding and A. P.Johnson Evidence for the metalkarbene complex (98) of Scheme 7 comes from the finding that bicyclobutanes [e.g. (94)] and diazomethylpentenes [eg.(99)] give similar product distributions on treatment' 32 with (PhCN),PdCl (cf:ref. 128). The intermediacy of (100) [cf:Scheme 71 is supported by the isolation of epimeric methyl ethers (101) from treatment of (91) with either [(CO),RhCl] (ref. 133) or AgClO (ref. 129) in methanol. Also solvolysis of the mesylate (102) gives a similar product mixture to that obtained by treating (92) with silver ions while solvolysis of (103) gives products similar to those obtained from (94)with silver ions.'33 Paquette has provided evidence for the intermediacy of an 'argento- carbonium ion'130*134 (104)* in the rearrangement of l-methyltricyclo[4,1,0,02~7]-heptane (105) to 3-ethylidenecyclohexenes by a study of deuterium-isotope effects on the rate of this rea~ti0n.l~~ He has also invoked intermediate argentocar- bonium ions to explain the steric course of Ag'-catalysed reactions of bicyclo- butanes (92) and (94),' 30 but these ideas have been criticized.' 33 H MeYAg 'R2 R' (102) R' = Me R2 = OMS (103) R' = OMS R2 = Me Ms = MeSO Among other noteworthy contributions are papers by Pettit' 35 and Grigg;' 36 syn-tricyclo-octane (106)rearranges rapidly in the presence of AgBF at 56 "C to give a 4 1 mixture of tetrahydrosemibullvalene (107) and cyclo-octa-1,5-diene whereas the anti-isomer (108)is stable for at least 5 days under these conditions ;l 35 a catalytic amount of [(CO),RhCl] converts cyclo-octatetraene monoepoxide 13' M.Sakai and S. Masamune J. Amer. Chem. SOC.1971 93 4610. 133 M. Sakai H. H. Westberg H. Yamaguchi and S. Masamune J. Amer. Chem. Soc. 1971,93,461I. 134 L. A. Paquette Accounts Chem. Res. 1971 4 280; L. A. Paquette and S. E. Wilson J. Amer. Chem. SOC.,1971 93 5935. 135 J. Wristers L. Brener. and R. Pettit J. Amer. Chem. Sac. 1970 92 7499. 13' R. Grigg and G. Shelton Chem. Comm. 1971 1247; R. Grigg R. Hayes and A. Sweeney ihid. p. 1248. * This is formally equivalent to the metal-carbene complex suggested earlier by Gassman'2S (Scheme 7) although the distribution of charge in these intermediates will obviously vary with the nature of the metal and its ligands. Alicyclic Compounds 355 into (109) at -50 "C and cis-bicyclo[6,l,0]nonatrieneto cis-8,9-dihydroindene at 35 "C,l36 whereas the thermal rearrangements require higher temperatures and are less clean.Specific Lewis acid catalysis is invoked to explain the latter reactions.' 36 0 Several novel metal-catalysed cycloadditions have been discovered' ',' (Scheme 8). Norbornadienone has not been isolated because of its ready cyclo- reversion to carbon monoxide and benzene but a stable (at -5 "C) iron carbonyl complex (1 10)of this molecule has now been ~ynthesi2ed.l~~ 65 % 35 % I 16% 47 % CN 29 % ref. 137 71 % Reagents i CH,=CHCO,Me Ni(CH,=CHCN), 60 "C 3h; ii CH,=CHCN. Ni(CH,=CHCN), 70 "C 3h; iii Fe,(CO), 60 "C 40 h Scheme 8 13' R. Noyori T. Suzuki Y. Kumagai and H. Takaya J. Amu. C/wm. Snc. 1971 93 5894; R. Noyori T. Suzuki and H. Takaya ibid. p. 5896. 13* R.Noyori S. Makino and H. Takaya J. Amer. Chem. SOC.,1971 93 1272. 139 J. M. Landesberg and J. Sieczkowski J. Amer. Chem. SOC.,1971 93 972. B. T. Golding and A. P. Johnson A re-inve~tigation'~' of the reaction between bullvalene and Fe2(C0)9 has shown that as well as 20 % of the previously rep~rted'~' product (1 1 l) six other isomeric complexes are formed including (1 12) (major product) and (1 13). Changes in the 'H n.m.r. spectrum of (113) occur on warming from 10 to 45 "C and are most economically explained by postulating interconversion of enantio- meric forms via 1,2-shifts of Fe(C0)3 groupings. On heating complex (113) at 120 "C it rearranges quantitatively to (114) oia a 1,2-shift of C(2) to C(9). [14]Annulene reacts with (NH3)3Cr(C0)3 to give a complex (115)derived from its valence isomer tran~-6a,l2a-dihydro-octalene.'~~ Solutions of (1 15) re-generate [14]annulene on standing.Pericyclic Reactions.-Reactions of this type are thoroughly reviewed in Chap- ter 3 (Reaction Mechanisms Part ii). Conformation and Reactivity.-The factors governing the steric outcome of the reactions of cycloalkanones with hydrides and organometallic reagents continue to be investigated. t-Butylallylmagnesium bromide appears to be a useful aid in such investigations since its reaction with ketones (R'COR2) can lead to two isomeric products (116) and (117) and it is claimed that the product ratio (1 16):(117) provides a sensitive measure of the steric hindrance in the neighbour- hood of the carbonyl By this test the carbonyl groups of cyclopenta- none and trans-Zhydrindanone (ratios 65 and 50 respectively) are more hindered than those of cyclohexanone and acetone ( ratios 3 and 3.4 respectively).I4O R. Aumann Angew. Chem. Internat. Edn. 1971 10 188 189 190. 14' G. N. Schrauzer P. Glockner K. I. G. Reid and I. C. Paul J. Amer. Chern. SOC. 1970. 92. 4479. 14' K. Stockel F. Sondheimer T. A. Clarke M. Guss and R. Mason J. Amer. Chem. SOC.. 1971 93,2571. 143 M. Cherest H. Felkin and C. Frajerman Tetrahedron Letters 1971 379. Alicyclic Compounds 357 Me,C-CH=CH -CH Ho-c‘R 1R2 Me3C-CH-CH=CH,IR1R2C-OH (1 16) (1 17) The equatorial alcohol derived from addition of t-butylallylmagnesium bromide to 4-t-butylcyclohexanone is solely (1 18),’44indicating that steric strain is the im- portant factor impeding axial attack (‘steric approach control’).In contrast the ratio of axial products (119) :(120)is very small (1.3),which leads to the conclusion that torsional strain is the major factor impeding equatorial attack. Thus the steric outcome of additions of hydrides and Grignard reagents to cyclohexanones is ascribed to the net difference between the steric strain in the transition state leading to the equatorial alcohol and the torsional strain the transition state leading to the axial In marked contrast to the reaction of most methyl organometallic reagents with 4-t-butylcyclohexanone trimethylaluminium under certain conditions (ketone :AlMe = 1 :2 ; benzene solution) gives mainly the trans-alcohol (121).145 A six-centred transition state containing two molecules of trimethyl-aluminium is invoked as a possible explanation.Certain P-hydroxy-ketones such Ph OH Ph OH OH Me3C (121) (122) (123; R = Me or Ph) as (122) react stereospecifically with phenyl or methyl Grignard reagents to form the cis-diols (123).146This is attributed to initial formation of the chelate (124) which is then attacked on the less hindered face. A similar explanation is ad- vanced for the stereospecific conversion of (125) into (126). 144 M. Cherest and H. Felkin Terrahedron Lerfers 1971 383. 14’ E. C. Ashby and S. Yu Chem. Cnrnrn. 1971 351. 146 E. Ghera and S. Shoua Chem. Comm. 1971 398. B. T. Golding and A. P. Johnson Lithium dimethyl cuprate adds to 3,4-epoxycyclohexene to form (127) and the conjugate addition product (128).14’ The trans stereochemistry of the latter is the reverse of that expected from an SN2’ process.Lithium methyl gives no conjugate addition but instead the major product is benzene hydrate (129) from a base- induced isomerization reaction. The lithium-diethylamide-induced rearrange- ment of a series of propylidene-cycloalkane oxides (130) to allylic alcohols148 exhibits a marked regioselectivity the endocyclic olefin product (13 1) predominat-ing except when n = 6. In the latter case (132) is formed after a slower reaction. These results are interpreted in terms of a syn elimination mechanism via a specific cis-coplanar transition state (which would be energetically unfavourable when n = 6).I Me OH n = 4 5 7 8 or 12 Schleyer’s proposal149 that torsional strain is responsible for the exo selectivity in the reactions of various norbornyl derivatives has been que~tioned.’~~ A comparative study of the rates of base-catalysed deuterium exchange of the 14’ J. Staroscik and B. Rickborn J. Amer. Chem. SOC.,1971 93 3046; D. M. Wieland and C. R. Johnson ibid. p. 3047. R. P. Thummel and B. Rickborn J. Org. Chem. 1971 36 1365. 149 P. von R. Schleyer J. Amer. Chem. SOC.,1967 89 701. S. P. Jindal S. S. Sohoni and T. T. Tidwell Tetrahedron Letters 1971 779; S. P. Jindal and T. T. Tidwell ibid. 1971 783. Alicyclic Compounds bicyclic ketones (133) (134) and (135) shows that the relative rates are 2s shown.The authors contend that angle strain and non-bonded repulsions adequately account for these rates. Further evidence for the unimportance of torsional strain in these reactions comes from the finding that there is little difference in the relative rates of exchange for camphor (136) and 4-methylcamphor (137). If torsional strain were important this should be accentuated by the CH,-H interaction in (1 37). Me-Me& J '2.4 ZoMetJ t 0.58 0.61 (1 36) (137) On the other hand equilibration studies show that endo-1-methyl-2-cyano-bicyclo[2,2,l]hept-5-ene (1 38) is more stable than the corresponding exo-com- pound (139) by 0.39 kcal mol-' and this is attributed to a torsional CH,-CN interaction,lS1 which it is argued should be even larger in a transition state where the degree of eclipsing is greater.Acetoxymercuration of cis-3,5-dimethylcyclohexeneand 3,5,5-trimethylcyclo- hexene (followed by treatment with NaBH,) gives the C(3)-acetates (140) and (141) respectively as major products.152 It is suggested that this unexpected result is due to a torsional effect whereby the C(3)-pseudo-equatorial methyl group disfavours attack of acetate ion at C(2) by disdaining to let H(2) pass ref (WI. ' ' J. M. Mellor and C. F. Webb Tetrahedron Letters 197 1 4025. 15* D. J. Pasto and J. A. Gontarz J. Amer. Chem. SOC.,1971 93 6909. B. T. Golding and A. P. Johnson OAc Calculations by Schleyer and Bingham of the differences in strain energy between bridgehead carbonium ions and the corresponding hydrocarbons in most cases show an excellent correlation with experimental solvolysis rates of suitably functionalized derivatives.' s3 As one might expect systems with larger bridges are more reactive because there is less strain in attempting to form a planar carbonium ion.However the treatment breaks down for (143) which solvolyses lo9 times more slowly than predicted. Of the compounds studied (143) is unique in that it lacks a P-alkyl group or hydrogen atom which is trans-periplanar to the bond carrying the leaving group and it is suggested that this structural feature greatly assists ionization by hyperconjugative stabilization of the transition state Similar calculations of the relative reactivities of the various bridgehead positions of protoadamantane (144) predict a reactivity order (position 6 > 3 > 1 or 8) which accords with the finding that 6-bromoprotoadamantane is the sole bromination product.' 54 ?Ts Q (143) (145) X = ODNB (3,5-dinitrobenzoate) or OPNB (p-nitrobenzoate) Wiberg's outstanding work' 5s on the solvolysis of derivatives of strainea bicycloalkanes has now been extended to the 3,5dinitrobenzoates of the isomeric bicyclo[6,l,0]nonan-2-ols[cf (145)I.l56*157 An explanation of the relative rate constants found [for solvolysis at 100 "C in 80 % aqueous acetone trans'trans-(1 43 krel 18 200 ; trans,cis-( 149 krel I ; cis,trans-(149 krel 65 ;cis,cis-(145) kre 14101 requires a careful consideration of subtle conformational factors in the molecules concerned.Thus Gassman s~ggests'~' that in trans,cis-(145) the R. C. Bingham and P. von R. Schleyer J. Amer. Chem. Soc. 1971,93 3189. '" A. Karim M. A. McKervey E. M. Engler and P. von R. Schleyer Tetrahedron Letters 1971 3987. 155 K. B. Wiberg R.A. Fenoglio and V. Z. Williams J. Amer. Chem. SOC.,1970 92 568 and references therein. 156 K. B. Wiberg and T. Nakahira J. Amer. Chem. Soc. 1971 93 5193. 15' P. G. Gassman E. A. Williams and F. J. Williams J. Amer. Chem. Soc. 1971 93 5199; for a related study cf P. G. Gassman J. Seter and F. J. Williams ihid. p. 1673. Alicyclic Compounds 36 1 H H 4opNB 4H (146) (147) bPNB leaving group lies astride a cyclopropyl bond [as in (146)] and participation is not possible whereas in trans,trans-( 145) the leaving group is trans to a cyclopropyl bond and participation occurs [as in (147)l.Last year we reported [Annual Reports (B) 1970,67,388] that the cycloaddition of unsymmetrical ketens to cyclopentadiene is usually highly stereoselective. It now seems that this is not the case with most other olefins,' s8 and the anomalous behaviour of cyclopentadiene is attributed to its planarity. Elimination reactions of alicyclic compounds have been reviewed.' 59 Miscellaneous Reactions.-Carbocyclic ring contractions,' 6o thermal addition of carbon<arbon multiple bonds to strained carbocyclics,' ' photochemical transformations of small-ring carbonyl compounds,' 62 and the chemistry of adamantane~'~ and cyclopropanones' 63 have all been reviewed.Triallylborane adds to 1-methylcyclopropene to give the product of cis-addition across the double bond (148; R = H) and the ring-cleaved product (149).'64 With trL(2-butenyl)borane the product is (148; R = Me) indicating the possibility of a concerted reaction via a cyclic transition state. L"Z /I ! RCH=CHCH CH,CH= CHR CH=CH (148) (1 49) Certain masked cyclopropanones are readily converted into p-lactams as shown in Scheme 9. Whereas trialkylboranes do not usually react with olefins the photochemically induced cis-addition of tri-n-alkylboranes to cyclohexenes has been accom-15' W. T. Brady F. H. Parry tert. and J. D. Stockton J. Org. Chem. 1971 36 1486; W. T. Brady and R. Roe jun. J. Atner. Chem. Soc. 1971 93 1662. 159 N.A. Lebel Adu. Alicyclic Chern. 1971 3 195. Ih0 D. Redmore and C. D. Gutsche Adu. Alicyclic Chem. 1971 3 1. '" P. G. Gassman Accounts Chem. Res. 1971 4 128. 'b2 A. Padwa Accounts Chem. Res. 1971 4,48. lb3 N. J. Turro R. B. Gagosian S. E. Edelson T. R. Darling J. R. Williams and W. B. Hammond Trans. N. Y. Acad. Sci. 1971 33 396. Yu. N. Bubnov 0. A. Nesmeyanova T. Yu. Rudashevskaya B. M. Mikhailov and B. A. Kazansky Tetrahedron Letters 1971 2153. 362 B. T. Golding and A. P. Johnson c1 I R = C,H Bun Bus Bu' or CH,-CH I CO Et Ref. 166. 95% when X = OH Y = OMe X=Y=N fi orX=OH,Y=N LJ or X = OH Y = OMe Reagents i Me,COCI; ii Ag+;iii NaN, pH 5.5 Scheme 9 pli~hed,'~'e.g. (150) gives (151) with triethylborane. Cyclo-octa-2,7-dienone behaves similarly but cyclopentene cyclo-octene and cyclododecene do not which supports the postulated intermediacy of a highly reactive trans-cycloalkene.R = H or Et Tricyclic cyclopropanols of the type (152) are readily available by metal- ammonia reduction of ketones such as (153).16* As shown in Scheme 10 these cyclopropanols can be made to undergo stereospecific rearrangements to give high yields of a variety of bicyclic systems. 165 H. H. Wasserman and M. S. Baird Tetrahedron Letters 1971 3721. '66 H. H. Wasserman H. W. Adickes and 0. E. de Ochoa J. Amer. Chern. SOC.,1971 93 5586. 16' N. Miyamoto S. Isiyama K. Utimoto and H. Nozaki Trtruhedrarz Letters 1971 4597. 168 P. S. Venkataramani and W. Reusch Tetrahedron Letters 1968 5283.Alicyclic Compounds Ref. 169 '0 Reagents i toluene-p-sulphonic acid-benzene reflux or alternatively KOH-MeOH ; ii NaH-benzene; iii MeOH ; iv toluene-p-sulphonyl chloride-pyridine ; v HOAc Scheme 10 169 P. S. Venkataramani J. E. Karoglan and W. Reusch J. Amer. Chem. SOC. 1971 93 269; K. Grimm P. S. Venkataramani and W. Reusch ibid. p. 270.